Salmonella are facultative intracellular pathogens which cause significant diseases in humans and animals. These organisms cause several disease syndromes, including enteric (typhoid) fever, gastroenteritis, bacteremias and focal infections. This grant proposes to study a murine infection with S. typhimurium and infection of macrophages and cultured epithelial cells with S. typhimurium and S. typhi. A set of virulence genes, termed Salmonella translocated effectors, that are translocated across the phagosome membrane into the eukaryotic cell cytoplasm by a type III secretion system encoded on the Salmonella pathogenicity island II will be studied. This grant proposes to further define these proteins and to study in molecular detail their role in virulence.